Interferon α (IFNα; hereinafter interferon is abbreviated to “IFN”) and interferon β (IFNβ) are known as type 1 IFNs with antiviral or anti-tumor activity. In addition, IFNα has been shown to be involved in autoimmune diseases. For example, aberrant production of IFNα has been reported in patients with the autoimmune diseases listed below. Neutralization of IFNα has also been suggested to relieve autoimmune symptoms.
systemic lupus erythematosus (Shiozawa et al., Arthr. & Rheum. 35, 412, 1992)
rheumatoid arthritis (Hopkins et al., Clin. Exp. Immunol. 73, 88, 1988)
Furthermore, cases where symptoms of autoimmune diseases have developed or been exacerbated by administration of recombinant IFNα2 have also been reported (Wada et al., Am. J. Gastroenterol. 90, 136, 1995; Perez et al., Am. J. Hematol. 49, 365, 1995).
IFNα has been shown to induce the differentiation of dendritic cells. Dendritic cells are also antigen-presenting cells. The induction of dendritic cell differentiation is thus thought to constitute an important mechanism in autoimmune diseases. Indeed, a close correlation has been suggested between the induction of dendritic cell differentiation by IFNα and the onset of systemic lupus erythematosus (Blanco et al., Science, 16: 294, 1540-1543, 2001). Thus, IFNα is suggested to show close links with autoimmune diseases as well as anti-tumor activity.
Meanwhile, IPCs were identified as cells that produce large quantities of type 1 IFNs upon viral infection. Very few IPCs exist in the blood. IPCs are thought to accounts for 1% or less of peripheral blood lymphocytes. However, IPCs have an extremely strong IFN-producing ability. The ability of IPCs to produce IFNs is as much as 3000 pg/ml/106 cells, for example. Thus despite their small numbers, IPCs can be said to produce the majority of IFNα and IFNβ in the blood.
IPCs are undifferentiated lymphocytic dendritic cells that are positioned as precursor cells of dendritic cells. IPCs are also called plasmacytoid dendritic cells. When stimulated with viruses, IPCs differentiate into dendritic cells that induce the production of IFN-γ and IL-10 by T cells. IPCs also differentiate into dendritic cells when stimulated with IL-3. Such dendritic cells that differentiated upon stimulation with IL-3 induce the production of Th2 cytokines (IL-4, IL-5, and IL-10) by T cells. As described above, IPCs have the property of differentiating into different types of dendritic cells depending on the type of stimulation.
Thus, IPCs are cells with two aspects: they are IFN-producing cells, and also dendritic cell precursor cells. Both cells play important roles in the immune system. Therefore, IPCs are important cells that contribute to the immune system in various ways.    [Non-patent Document 1] Shiozawa et al., Arthr. & Rheum. 35, 412, 1992    [Non-patent Document 2] Hopkins et al., Clin. Exp. Immunol. 73, 88, 1988    [Non-patent Document 3] Wada et al., Am. J. Gastroenterol. 90, 136, 1995    [Non-patent Document 4] Perez et al., Am. J. Hematol. 49, 365, 1995    [Non-patent Document 5] Blanco et al., Science, 16:294, 1540-1543, 2001